Synthesis, Conformational Analysis and Evaluation of the 2-aryl-4-(4-bromo-2-hydroxyphenyl)benzo[1,5]thiazepines as Potential α-Glucosidase and/or α-Amylase Inhibitors.

The ambident electrophilic character of the 5-bromo-2-hydroxychalcones and the binucleophilic nature of 2-aminothiophenol were exploited to construct the 2-aryl-4-(4-bromo-2-hydroxyphenyl)benzo[1,5]thiazepines. The structures and conformation of these 2-aryl-4-(4-bromo-2-hydroxyphenyl)benzo[1,5]thiazepines were established with the use of spectroscopic techniques complemented with a single crystal X-ray diffraction method. Both 1H-NMR and IR spectroscopic techniques confirmed participation of the hydroxyl group in the intramolecular hydrogen-bonding interaction with a nitrogen atom. SC-XRD confirmed the presence of a six-membered intramolecularly hydrogen-bonded pseudo-aromatic ring, which was corroborated by the DFT method on 2b as a representative example in the gas phase. Compounds 2a (Ar = -C6H5), 2c (Ar = -C6H4(4-Cl)) and 2f (Ar = -C6H4(4-CH(CH3)2) exhibited increased inhibitory activity against α-glucosidase compared to acarbose (IC50 = 7.56 ± 0.42 µM), with IC50 values of 6.70 ± 0.15 µM, 2.69 ± 0.27 µM and 6.54 ± 0.11 µM, respectively. Compound 2f, which exhibited increased activity against α-glucosidase, also exhibited a significant inhibitory effect against α-amylase (IC50 = 9.71 ± 0.50 µM). The results of some computational approaches on aspects such as noncovalent interactions, calculated binding energies for α-glucosidase and α-amylase, ADME (absorption, distribution, metabolism and excretion) and bioavailability properties, gastrointestinal absorption and blood-brain barrier permeability are also presented.

Correction: A convenient domino Ferrier rearrangement-intramolecular cyclization for the synthesis of novel benzopyran-fused pyranoquinolines.

Correction for 'A convenient domino Ferrier rearrangement-intramolecular cyclization for the synthesis of novel benzopyran-fused pyranoquinolines' by Paseka T. Moshapo et al., Org. Biomol. Chem., 2016, DOI: 10.1039/c5ob02536b.

A convenient domino Ferrier rearrangement-intramolecular cyclization for the synthesis of novel benzopyran-fused pyranoquinolines.

The Ferrier rearrangement and the Povarov reaction have proven indispensable tools in carbohydrate chemistry and the synthesis of N-heterocycles, respectively. We hereby report a one-pot cyclization sequence involving the Ferrier and Povarov-like reactions in the synthesis of novel pentacyclic N-heterocycles: benzopyran-fused pyranoquinolines. The reaction entails three component condensation of a glycal with a variety of anilines and 2-hydroxybenzaldehydes under Lewis acid catalysis to yield the title compounds in 4-24 hours of reaction time, in moderate to high yields and excellent diastereoselectivity. Of the Lewis acid catalysts deployed [Sc(OTf)3, Al(OTf)3, Cu(OTf)2, CuOTf, I2, InCl3, and La(OTf)3] in various solvents (acetonitrile, THF, dichloromethane, 1,2-dichloroethane and diethyl ether) at room and elevated temperatures, Sc(OTf)3 (10 mol%) in acetonitrile at 70 °C gave the best results, with excellent diastereoselectivity. CAN-mediated oxidative ring opening of the pentacyclic N-heterocycle gave the corresponding enantiometrically pure chromenoquinoline bearing a pendant sugar moiety.